In this proposal we plan to delineate the solution conformational dynamics, features and properties of the bizarre 5'-terminus of mouse myeloma mRNA by a combination of 1H, 1H-(31p), 31p, 31P-(1H), 13C, 13C-(1H) and 13C-(31P) NMR studies of the segments which constitute the 5'-terminus. Studies will undoubtedly reveal information about the stereodynamics of the molecular framework of the 5'-terminus of myeloma mRNA, but in addition will shed considerable light about the conformational properties of the 5'-terminus of mRNAs from several viruses including reovirus because the unusual 5'-terminus encountered in myeloma mRNA is a general feature of mRNAs of many viruses. At the very heart of the problem lies the fundamental observation that Nature creates - either during normal biogenesis or during the onset of disease - polynucleotides from common nucleotides and it imparts differences by carefully engineered modifications which prima facie appear to be minor, but have profound and spasmodic impact on conformation. The studies will reveal the nexus between constitutional modification and conformational properties and the information is very relevent to the fact that many chemotherapeutic and anticancer agents are modified derivatives of nucleic acid components.